Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol

Abstract

This evidence supports a hypothesis that stop and go processes are under control of distinct neurochemical mechanisms.

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

“…The mixed D1/D2 receptor antagonist, cis-flupenthixol, had no effect on action cancellation, but perhaps more critically, it did not influence the SSRT-decreasing effects of methylphenidate and modafinil at doses that significantly increased the GoRT (Eagle et al 2007). This is perhaps the most convincing evidence to date that D1 and D2 receptors play little role in the mediation of SSRT.…”

“…In both humans and rodents, Damphetamine decreased SSRT only when subjects had relatively slow baseline SSRT (de Wit et al 2000;Feola et al 2000). Similar effects can be seen for methylphenidate (Boonstra et al 2005;Eagle et al 2007), and modafinil in both human and rat (Eagle et al 2007;Turner personal communication). Baseline-dependent psychostimulant action was also found in a rodent study within which the SSRT was artificially manipulated (rather than the natural within-population variability considered above).…”

“…Modafinil is of particular interest to this review as its effects appear to be highly specific to action cancellation. Modafinil has no effects on either the go process (GoRT) or the no-delay, action-restraint component of the stopsignal task (Eagle et al 2007;Turner et al 2004), unlike conventional psychostimulants which often speed GoRT and SSRT (Bedard et al 2003;Lijffijt et al 2006;Tannock et al 1989). From a translational perspective, modafinil similarly improves SSRT in rats and humans (Eagle et al 2007;Turner 2006;Turner et al 2003Turner et al , 2004, effects that are directly comparable with the effects of conventional psychostimulants.…”

“…Recently, within one basic task framework, the SSRT has been measured alongside stop-trial commission errors (measured under a condition when the go and stop signals were presented together, the no-delay or zero-delay condition) (e.g. Eagle and Robbins 2003a;Eagle et al 2007;Rubia et al 2001;Schachar et al 2007). Examining action restraint and action cancellation in this way eliminates potentially confounding effects of comparing between different tasks and may provide a more practical framework for further analysing these forms of inhibition.…”

“…b No effect on SSRT of intraperitoneally administered citalopram in a within-subjects (n=26) treatment (dose F(4,100)=0.23, n.s.). Methodology in b was identical to that described in Eagle et al (2007) with drugs administered following a randomised Latin square design. c and d Significant effects of atomoxetine on SSRT in c human and d rat subjects.…”